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Structural insight into TRPV5 channel function and modulation.

ABSTRACT: TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodiscs, as well as of a TRPV5 W583A mutant and TRPV5 in complex with CaM. These structures highlight the mechanism of calcium regulation and reveal a flexible stoichiometry of CaM binding to TRPV5.

SUBMITTER: Dang S

PROVIDER: S-EPMC6500171 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Structural insight into TRPV5 channel function and modulation.

Dang Shangyu S van Goor Mark K MK Asarnow Daniel D Wang YongQiang Y Julius David D Cheng Yifan Y van der Wijst Jenny J

Proceedings of the National Academy of Sciences of the United States of America 20190411 18

TRPV5 (transient receptor potential vanilloid 5) is a unique calcium-selective TRP channel essential for calcium homeostasis. Unlike other TRPV channels, TRPV5 and its close homolog, TRPV6, do not exhibit thermosensitivity or ligand-dependent activation but are constitutively open at physiological membrane potentials and modulated by calmodulin (CaM) in a calcium-dependent manner. Here we report high-resolution electron cryomicroscopy structures of truncated and full-length TRPV5 in lipid nanodi ...[more]

PMID: 30975749

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